Before the development of the modern chemical and pharmaceutical industries, essential oils were used in many areas of daily life as antiseptic and disinfectant materials in pharmaceutical and cosmetic applications, such as anti microbial (antiviral, antibacterial and antifungal) and larvicidal agents. Essential-oil-based formulations with a broad spectrum of antimicrobial activity have been shown to be relatively nontoxic to mammals, particularly to surface cleaning compositions based on essential oils that were particularly effective disinfectants and antimicrobials have been replaced with more potent synthetic chemicals and antibiotics, are cheaper and highly effective and can be used in lower concentrations. With time, however, the toxic and environmental effects of such synthetic chemicals have been revealed, and there is now an effort to replace them with the same essential oil agents that they replaced.
In the area of disinfectants for consumer products a safe alternative for synthetic chemicals and antibiotics used as disinfectants and antimicrobial agents are needed to replace chemicals now used which have been shown to be toxic to man and to the environment. Some of these disinfectants have been shown due to have chronic toxic effects, especially in children. There is a need to replace chemicals containing active chlorine and other synthetic chemicals with nontoxic natural “green” materials. Fragrant natural essential oils with little or no toxicity have shown good anti-microbial properties and, as such, are contenders for replacing chlorine-containing disinfectants. We have demonstrated for eucalyptus oil good anti-microbial activity in a laundry softening application. The failure, however of essential oil products, including current encapsulated formulations, to break into the consumer market is due to raw material prices, insufficient sustained activity, and the need for repeated application.
In the area of pesticides the present microcapsules can be used in such applications as larvicides, repellents and insecticides. With respect to larvicide applications the essential oil microcapsules for mosquito control will compete with state of art larvicidal agents [organophosphates, organochlorines, carbamates, petroleum oils, insect growth regulators (IGR) (e.g., methoprene or pyriproxyfen.
Two important reasons to control mosquitoes are to avoid nuisance biting, and to preclude the spread of mosquito-borne diseases including illnesses such as malaria, encephalitis, dengue and yellow fevers, as well as West Nile Virus. The World Health Organization estimates that more than 500 million clinical cases each year are attributable to disease agents carried and transmitted by mosquitoes. In the United States there is a recent upsurge in mosquito borne diseases which has significantly increased the commercial value of larvicides. Currently, chemical insecticides are used to control mosquitoes either as larvicide or as adulticide, even though insecticides may be detrimental to human health and are known to have harmful effects on the environment and wildlife. Biological mosquito larvicides are mainly microorganism-based products that are registered as pesticides for control of mosquito larvae outdoors. In addition to being costly, biologicails are difficult to apply efficiently because the duration of effectiveness depends primarily on the formulation of the product, environmental conditions, water quality, and mosquito species.kly 2% sprays of mineral oils.
Applications Claimed for the Use of the Invented Microcapsules:
Nontoxic larvicides, Cleaners for hard surfaces, Laundry detergents, diapers, feminine tampons Laundry softeners. Insect repellents especially to mosquitoes, and ants.
The following applications are claimed for the invented microcapsules of essential oils. The use of the microcapsules of the present invention in the given application increase the efficacy of the essential oil by lowering the quantity needed for prolonged activity thus lowering the cost of application and making the essential oil competitive with current synthetic chemicals.    1) Disinfectant and sanitizing compositions for hard surfaces such as counter tops, tiles, porcelain products (sinks and toilets), floors, windows, cutlery, glassware, dishes and dental and surgical instruments;    2) Fragrance and skin-benefit liquids for application to textile structures to improve physiological conditions of the skin;    Antimicrobial wipes that provide improved immediate germ reduction covered in the following US patents described in the section Comparison with Current State of Art for essential oils;    3) Leave-on antimicrobialcompositions that provide improved residual benefit covered in the following US patents described in the section Comparison with Current State of Art for essential oils, versus gram positive bacteria;    4) Antimicrobial compositions formulated with essential oils covered in the following US patents described in the section Comparison with Current State of Art for essential oils;    6) Disinfectant and sanitizing compositions based on essential oils covered in the following US patents described in the section Comparison with Current State of Art for esseritial oils;    7) Blooming agents in germicidal hard surface cleaning compositions;    8) Liquid detergent compositions;    9) Antimicrobial compositions with antiseptic, antiviral and larvicidal activity as treatments for cold sores, head lice, vaginal thrush, verruca, warts, and athlete's foot and as antimicrobial mouth washes and surface cleaners;    10) Lice treatment;    11) Natural pesticides;    12) Flavoring agents;    13) Fragrances;    14) Treatment of infections in man and animals;    15) Lice repellant composition;    16) Analgesic and antiphlogistic compositions;    17) Fragrance or insect-repellant agent;    18) Active agents in pharmaceuticals and cosmetics;    19) Benefit agent in extruded soap and/or detergent bars;    20) Food or tobacco additive;    21) Active agents in Pharmaceuticals and Cosmetics;    22) Hair care products; and    23) Dentifrice containing encapsulated flavoring.    24) Mosquito, ants and insect repellents    25) Mosquito larvicides    26) Anti viral agents    27) Anti fungal agents    28) Gels against gum diseases    29) Tampons for women use safe from toxic syndromes    30) DiapersComparison with Current State of Art
A review of the state of art shows that essential oils have been incorporated into many different formulations for the above-described applications. Although the encapsulation techniques have been used for such oils to improve stability, facilitate sustained release, and reduce application costs (for the same applications that we propose to develop), these efforts have, to the best of our knowledge, not resulted in commercial products that can effectively compete with currently available synthetic chemicals. The reason is that currently used essential oils, including those that have been encapsulated, do not meet one or more of the requirements described above for producing a cost-effective microencapsulated product. The drawbacks of currently available products include:    1) They do not have sufficiently long life times on the surfaces to which they are applied and/or do not give sustained released on those substrates at a continuous effective dose because of ineffective encapsulating barriers;    2) They are produced by a process that destroys or modifies many of the oil's properties; and    3) In many cases, they must be applied at a higher than cost-effective dosage to be effective and thus cost significantly more than currently available synthetic chemicals.
The patent literature on encapsulated essential oils can be divided into the following categories:    1) Patents describing all methods of encapsulation and a wide range of polymer encapsulants but giving limited examples and claims;    2) Patents based on a solid core containing the essential oils adsorbed inside, with and without subsequent coatings;    3) Encapsulation of essential oil droplets or emulsions in a polymer shell by coacervation or adsorption of preformed polymers;    4) Encapsulation of essential oil droplets or emulsions in a polymer shell by coacervation or adsorption of preformed polymers; and    5) Encapsulation in microorganisms. The closes state of art in the present patent is the encapsulation of essential oils as an a liquid core. In patents U.S. Pat. No. 3,957,964, U.S. Pat. No. 5,411,992, U.S. Pat. No. 6,414,036 describing all methods of encapsulation and a wide range of polymer encapsulants but giving limited examples and claims. None of the examples or claims relate specifically to interfacial polymerization to form polyurethanes or polyurea encapsulated essential oils.
In U.S. Pat No. 6,238,677, U.S. Pat. No. 5,753,264, U.S. Pat. No. 6,200,572, PCT/PUBLICATION-1997-07-09, A1 on the encapsulation of essential oil droplets or emulsions in a polymer shell by coacervation or adsorption of preformed polymers. These patents are not relevant to our proposed patents and practically would not have the necessary sustained release or required stability in our applications because of the nature of the microcapsule Walls.
In U.S. Pat. No. 5,232,769 pertains to the encapsulation of essential oil droplets or emulsions in a polymer shell by interfacial polymerization of monomers such as melamine or urea dissolved in essential oil droplets and cross-linked interfacially by formalin. There is no sustained release in this case, and the microcapsules in the formalin, melamine or urea example are hard and would give an unpleasant sensation to a surface to which it was applied.
Interfacial polymerization to form polyurea and polyurethane microcapsules have been widely applied to the encapsulation of pesticides and herbicides [see A. Markus, Advances in the technology of controlled release pesticide formulations” in Micro-encapsulation: Methods and Industrial Applications, S. Benita (Ed), 1996, pp. 73-91 and U.S. Pat. No. 4,851,227 Jul. 25, 1989]. These methods and materials have not been used however in the encapsulation of the essential oils and it is indeed surprising that they work well for non-toxic essential oils. Use of interfacial condensation to encapsulate substances such as pharmaceuticals, pesticides and herbicides is discussed in U.S. Pat. No. 3,577,515, issued on May 4, 1971. The encapsulation process involves two immiscible liquid phases, one being dispersed in the other by agitation, and the subsequent polymerization of monomers from each phase at the interface between the bulk (continuous) phase, and the dispersed droplets. The immiscible liquids are typically water and an organic solvent. Polyurethanes and polyureas are included in the types of materials suitable for producing the microcapsules. The use of emulsifying agents (also known as suspending or dispersing agents) is also discussed. The United States patent discloses formation of microcapsules comprising a polymeric sphere and a liquid centre, ranging from 30 micron to 2 mm in diameter, depending on monomers and solvents used.
Use of interfacial condensation to encapsulate substances such as pharmaceuticals, pesticides and herbicides is discussed in U.S. Pat. No. 3,577,515, issued on May 4, 1971. The encapsulation process involves two immiscible liquid phases, one being dispersed in the other by agitation, and the subsequent polymerization of monomers from each phase at the interface between the bulk (continuous) phase, and the dispersed droplets. The immiscible liquids are typically water and an organic solvent. Polyurethanes and polyureas are included in the types of materials suitable for producing the microcapsules. The use of emulsifying agents (also known as suspending or dispersing agents) is also discussed. The United States patent discloses formation of microcapsules comprising a polymeric sphere and a liquid centre, ranging from 30 micron to 2 mm in diameter, depending on monomers and, solvents used.
United Kingdom Patent No. 1,371,179 discloses the preparation of polyurea capsules for containing dyes, inks, chemical reagents, pharmaceuticals, flavouring materials, fungicides, bactericides and pesticides such as herbicides and insecticides. The capsules are prepared from various di- and polyisocyanates in a dispersed organic phase. Some of the isocyanate present reacts to yield an amine which reacts further with remaining isocyanate at the interface with water and subsequently polymerizes to form a polyurea shell. The aqueous phase also contains a surfactant, for example an ethoxylated nonylphenol or a polyethylene glycol ether of a linear alcohol. In addition, the aqueous phase contains protective colloids, typically polyacrylates, methylcellulose and PVA. Particle sizes as low as 1 micron are exemplified. Encapsulation of insect hormones and mimics are among the systems mentioned.
U.S. Pat. No. 4,046,741 and U.S. Pat. No. 4,140,516 appear to relate to developments of the process disclosed in United Kingdom Patent No. 1,371,179. According to U.S. Pat. No. 4,046,741, a problem with microcapsules is instability caused by evolution of carbon dioxide from residual isocyanate entrapped the microcapsules. U.S. Pat. No. 4,046,741 discloses a post-treatment of polyurea microcapsules with ammonia or an amine such as diethylamine. This removes the residual isocyanate, allowing subsequent storage of the microcapsules at lower pH's without generation of carbon dioxide. U.S. Pat. No. 4,140,516 discloses the use of quaternary salts as phase transfer catalysts to speed up the formation of polyurea microcapsules.
Canadian Patent No. 1,044,134 is concerned with micro-encapsulation of insecticides, particularly pyrethroids. The insecticide is dissolved, together with a polyisocyanate, in a water-immiscible organic solvent. The solution in organic solvent is then dispersed in water by agitation, and a polyfunctional amine is added while agitation is continued. The polyisocyanate and the polyfunctional amine react to form a polyurea shell wall that surrounds the dispersed droplets containing the insecticide.
Micro-encapsulation (or encapsulation) of active agents is a well-known method to control their release and improve shelf life and duration of activity. Sustained release formulations based on encapsulation of the active agent can produce a more cost effective product than the non-encapsulated product. Many other hydrophobic or non-water soluble agents such as pesticide have been successfully encapsulated by a variety of methods. Microcapsules are flowable powders or powders having particle diameters in the range of approximately 0.1 microns to 1,000 microns. They are prepared using a range of coating processes in which finely distributed solid, liquid and even gaseous substances are used. Polymers are conventionally used as the coating or wall material. Basically, microcapsules therefore consist of two disparate zones, the core zone and the coating zone. Preparation processes that are suitable for micro-encapsulation include: phase separation processes (simple and complex coacervation), interface polymerization processes (polycondehsation or polyaddition from dispersions) and physicomechanical processes (fluidized-bed process, spray drying). An essential disadvantage of conventional micro-encapsulation is the fact that the preparation is relatively complicated.
The encapsulation of materials such as medications, pesticides (including insecticides, nematocides, herbicides, fungicides and microbiocides), preservatives, vitamins, and flavoring agents is desirable for a number of reasons. In the case of medicatioris and pesticides, encapsulation may provide controlled release of the active material. In the case of vitamins, the encapsulation may be carried out to protect the vitamin from oxidation and thus to extend its shelf life. In the case of a flavoring agent, encapsulation may be carried out to place the flavoring agent in an easily metered form, which will release the flavoring agent in response to a controllable stimulus, such as the addition of water. It is generally known to skilled practitioners in the field of flavor encapsulation that current practical commercial processes for producing stable, dry flavors are generally limited to spray drying and extrusion fixation. The former process requires the emulsification or solubilization of the flavor in a liquid carrier containing the encapsulating solids, followed by drying in a high-temperature, high-velocity gas stream and collection as a low-bulk-density solid.
While spray drying accounts for the majority of commercial encapsulated materials, several limitations of the process are evident. Low-molecular-weight components of complex or natural flavor mixtures may be lost or disproportionate during the process. The resultant flavor-carriers are porous and difficult to handle. In addition, deleterious chemical reactions such as oxidation can result on surfaces exposed during and after drying. The final product, a dry free-flowing powder, will release the encapsulant rapidly upon rehydration whether rapid release is desired or not.
There are encapsulated forms of larvicides based on materials other than essential oils. For example ALTOSID® by Wellmark International is a micro-encapsulated mosquito larvicide has been used in the United States to reduce mosquito infestations by preventing immature mosquito larvae from becoming disease-spreading adults. The active ingredient, methoprene, is an insect growth regulator that interferes with normal mosquito development.
Microcapsule Characteristics of the Invention
Encapsulation is needed for sustained release and improved stability of essential oils, both characteristics that are required to make a product cost effective. Products based, on essential oils may be extremely sensitivity to oxidation and volatile, properties that impair their efficacy and encapsulation is needed to prevent oxidation and evaporation. Many “green” materials, including essential oils, are less efficient and more expensive than the synthetic chemicals they seek to replace. There is thus a need to produce these “green” materials with a smaller effective dosage and increased effectiveness by enhancing the duration of activity per dose. The products that we are proposing are sustained release formulations will meet these needs in the form of encapsulated essential oils. When applied to a given substrate the oils will be released at a constant rate over a long period of time, thus increasing the duration of activity per dose and lowering the quantity needed and hence reducing the cost of the product. The encapsulation also will stabilize the essential oils with respect to oxidation and evaporation, a step that is required for product formulation, shelf life, application and duration of activity upon application.
The invented microcapsules are micron-sized microcapsules containing a liquid core of essential oil by a cost-effective process that has a high encapsulation efficiency with low oil loss. The resultant microcapsules release an effective dose at a constant unchanging rate (termed zero order release) giving a longer duration of activity than the same quantity of non-encapsulated oil: The above requirements will be met by our room-temperature interfacial formation of microcapsules from reagents that form polyurea or polyurethane films around dispersed oil droplets. The tough thin polyurea or polyurethane film's permeability is readily controlled by the conditions of polymerization, the composition of the reactants and the catalysts. The resultant materials are nontoxic and ultimately biodegradable.
The are many requirements needed for a micro-encapsulated essential oils formulation to be competitive, are met by the invented room-temperature interfacial formation of microcapsules from reagents that form polyurea or polyurethane films around dispersed essential oil droplets. The following requirements must be met:    1) Microcapsules must have a spherical shape, this gives the smallest surface area per unit volume that provides both efficient controlled-sustained release and maximum flow properties;    2) A nanometer to micron size is required for the capsules in order to produce an appealing homogenous readily applied formulation that does not have an unaesthetic grainy appearance or touch upon application to a given surface;    3) A microcapsule should comprise a thin external polymer membrane encapsulating a liquid core of essential oil. The polymer membrane controls the release of the oil and prevents it from being oxidized or evaporating. This configuration of liquid core encapsulated within a spherical membrane allows for an ideal constant and sustained release pattern (termed zero-order release);    4) The crosslinking density and hydrophobic/hydrophilic balance of the encapsulating membrane should be tailored to provide the required duration of control release;    5) The encapsulating membrane should be tough but not brittle to facilitate mechanical processing and to impart a smooth feel to a surface, as is required in some applications for hard surfaces and textiles;    6) Low- or room-temperature formation of the microcapsules in aqueous solutions is required to prevent alteration of oil properties at elevated temperatures and to minimize product costs;    7) Micro-encapsulation provides the surface properties such as the charge required for adsorption; and    8) To facilitate the conferring of regulatory status the encapsulating membrane and reagents used in the product should be inexpensive so as to give an economical product) non-carcinogenic and non-teratogenic and free of heavy metals.
These above-described requirements are met by our process of interfacial formation of the microcapsules using reagents that form polyurea or polyurethane membranes around dispersed oil droplets or emulsions at room temperature in aqueous solutions. The same requirements are not, however, met by the currently available techniques.